Negative effect of vitamin D on kidney function: a Mendelian randomization study.
Nephrol Dial Transplant
; 33(12): 2139-2145, 2018 12 01.
Article
in En
| MEDLINE
| ID: mdl-29718335
ABSTRACT
Background:
The kidney plays a central role in the regulation of vitamin D metabolism. It is not clear, however, whether vitamin D influences kidney function. Previous studies have reported conflicting results, which may have been influenced by reverse causation and residual confounding. We conducted a Mendelian randomization (MR) study to obtain unconfounded estimates of the association between genetically instrumented vitamin D metabolites and estimated glomerular filtration rate (eGFR) as well as the urinary albumincreatinine ratio (UACR).Methods:
We performed a two-sample MR study based on three single nucleotide variants associated with 25(OH)D levels rs2282679, rs10741657 and rs12785878, related to the genes GC, CYP2R1 and DHCR7, respectively. Estimates of the allele-dependent effects on serum 25(OH)D and eGFR/UACR were obtained from summary statistics of published genome-wide association meta-analyses. Additionally, we performed a one-sample MR analysis for both 25(OH)D and 1,25(OH)2 D using individual-level data from six cohorts.Results:
The combined MR estimate supported a negative causal effect of log transformed 25(OH)D on log transformed eGFR (ß = -0.013, P = 0.003). The analysis of individual-level data confirmed the main findings and also revealed a significant association of 1,25(OH)2 D on eGFR (ß = -0.094, P = 0.008). These results show that a 10% increase in serum 25(OH)D levels causes a 0.3% decrease in eGFR. There was no effect of 25(OH)D on UACR (ß = 0.032, P = 0.265).Conclusion:
Our study suggests that circulating vitamin D metabolite levels are negatively associated with eGFR. Further studies are needed to elucidate the underlying mechanisms.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vitamin D
/
Polymorphism, Single Nucleotide
/
Mendelian Randomization Analysis
/
Glomerular Filtration Rate
/
Kidney
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Nephrol Dial Transplant
Journal subject:
NEFROLOGIA
/
TRANSPLANTE
Year:
2018
Type:
Article
Affiliation country:
Germany